This is a two-year application proposes to use a novel approach to determine the proliferative index of human tumor tissue to be used as a predictor of radiation responsiveness. The approach uses the in situ hybridization (ISH) technique to detect the cellular H3 mRNA in human tumor lesions. The expression of the cellular histone H3 gene is tightly coupled to the synthesis of DNA during the cell cycle. Through preliminary experiments we have established a list of criteria that will permit us to categorize pre-operative human oral cancer lesions as radio-sensitive or radio-resistant. This method will clearly reveal the proliferative index of the human oral tumor at the time of pre-operative biopsy. This approach has many advantages over existing methods to determine the proliferative index of human tumors. Furthermore, our method can be performed on archival materials, thus allow our hypothesis to be tested in a retrospectively. We propose to test the applicability of this approach by performing a correlative study of the in situ labelling of H3 mRNA of human oral cancers and radiation therapy responsiveness. We hypothesize that our method can be used reliably to determine the radiation responsiveness of human oral cancer lesions. Our hypothesis is based on an extensive body of preliminary data derived from human and hamster systems, and will employ experimental approaches already established in the laboratories of the applicants and their collaborators. Thus, the work has a high likelihood of providing important information regarding the potential applicability of this method to be used as a predictor for clinical radiation treatment.